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This article is part of the supplement: Kitasato Symposium 2011: Translational prospects for cytokines in 2011

Oral presentation

Natural Treg and role of IL-2 in lupus

Gabriela Riemekasten* and Jens Y Humrich

  • * Corresponding author: Gabriela Riemekasten

Author Affiliations

Department of Rheumatology and Clinical Immunology, Charité University hospital, Berlin, 10117, Germany

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Arthritis Research & Therapy 2011, 13(Suppl 2):O7  doi:10.1186/ar3411

The electronic version of this article is the complete one and can be found online at: http://arthritis-research.com/content/13/S2/O7


Published:16 September 2011

© 2011 Riemekasten and Humrich.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

Effector T cells play an important role in the pathogenesis of lupus. As recently shown in murine lupus, they contribute to tissue damage and glomerulonephritis.

Methods

The role of naturally occurring regulatory T cells (Treg) and of IL-2 was studied in vitro and in vivo by using flow cytometry and the NZB/W lupus mouse model.

Results

In healthy individuals as well as in young lupus prone mice without any signs of the disease, effector T cells are tightly controlled by naturally occurring regulatory T cells (Treg) that can be shown by different approaches: 1. After depletion of Treg cells by anti-CD25 therapy, murine lupus is strongly accelerated. 2. After passive transfer of Treg (CD4+CD25+ T cells consisting of 95% FoxP3+ T cells), murine lupus improved reflected by reduced proteinuria and increased survival compared to control mice [1]. 3. In vitro depletion of Treg lead to better detection of autoantigen-specific effector T cells with frequencies above the detection limit for flow cytometry. The frequency of autoangien-specific T cells correlate with the disease activity in human and murine lupus. The control of effector T cells by Treg cells can be also used for studying the phenotype of effector T cell and their function at an autoantigen-specific level. However; as shown in the murine NZB/W lupus model, there is a progressive loss of Treg/Tcon homeostasis during lupus development in different compartments with a progressive Treg deficiency. In lupus mice with proteinuria, the phenotype of effector T cells is very similar to the T cell phenotype obtained in IL-2 deficient mice. As known from the literature, IL-2 levels are decreased in SLE patients. According to the characteristics of Treg, they are more sensitive to IL-2 deficiency. Supporting this, addition of IL-2 resulted in a dominant proliferation of Treg cells. In murine lupus, IL-2 improved survival and decreased proteinuria in diseased NZB/W mice.

Conclusions

Our data support the possible role of Treg and of IL-2 supplementation in lupus therapy. Further studies are underway to evaluate IL-2 supplementation and its effects on immune cells and disease symptoms in lupus.

References

  1. Humrich JY, Morbach H, Undeutsch R, Enghard P, Rosenberger S, Weigert O, Kloke L, Heimann J, Gaber T, Brandenburg S, Scheffold A, Huehn J, Radbruch A, Burmester GR, Riemekasten G: Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus.

    Proc Natl Acad Sci USA 2010, 107(1):204-209. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL